1.Gut microbiota-derived tryptophan metabolites regulated by Wuji Wan to attenuate colitis through AhR signaling activation.
Wanghui JING ; Sijing DONG ; Yinyue XU ; Jingjing LIU ; Jiawei REN ; Xue LIU ; Min ZHU ; Menggai ZHANG ; Hehe SHI ; Na LI ; Peng XIA ; Haitao LU ; Sicen WANG
Acta Pharmaceutica Sinica B 2025;15(1):205-223
Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.
2.Inpatients with oral and maxillofacial military training injuries:a retrospective analysis
Jianzhen SHE ; Haitao KONG ; Luying YANG ; Fan SHI ; Lei TIAN ; Liang KONG ; Bolei CAI
Military Medical Sciences 2025;49(1):22-26
Objective To analyze the characteristics of oral and maxillofacial injuries from military training and provide references for related prevention and treatment.Methods A retrospective analysis was conducted of the medical records of 111 patients with oral and maxillofacial military training injuries treated between 2014 and 2023.Results From 2014 to 2023,the number of hospitalized patients with maxillofacial military training injuries in the hospital trended upward.The top 3 training injuries in the spectrum of diseases were maxillofacial fractures(45.08%),maxillofacial space infections(28.83%),and temporomandibular joint injuries(18.92%).The average number of hospitalizations for all maxillofacial military training injuries was 1.33(1-4),and the median length of hospital stay was 8(5,12)days.The median hospitalization cost was 14 793.23(5236.18,24 255.25)yuan,and the improvement rate was 95.50%.Conclusion The number of patients hospitalized due to oral and maxillofacial military training injuries in this hospital is increasing year by year,and the injuries are mostly jaw fractures.Precautions should be taken to prevent maxillofacial training injuries.
3.Mechanism of glioma stem cells with high expression of PTPRZ1 inducing TAMs polarization to M2 immunosuppressive phenotype
Lele AN ; Ying YANG ; Qing LIU ; Feiyue DOU ; Lujing WANG ; Yue CHENG ; Chao WANG ; Qianying RUAN ; Lei ZHOU ; Haitao GUO ; Weikai KONG ; Xuegang LI ; Chuan LAN ; Fei LI ; Yu SHI
Journal of Army Medical University 2024;46(8):796-803
Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.
4.Population survey of Pomacea spp. in Shandong Province and preliminary study on the risk of population infection with Angiostrongylus cantonensis
Yongbin WANG ; Jun LIU ; Haitao HAN ; Longjiang WANG ; Yuejin LI ; Lijun MA ; Benguang ZHANG ; Xiangli KONG ; Ge YAN ; Yunhai GUO ; Yan XU
Chinese Journal of Endemiology 2023;42(7):580-585
Objective:To study the population distribution of Pomacea spp. in Shandong Province and the risk of angiostrongyliasis cantonensis in the local population, and to provide a basis for scientific prevention and control of related diseases. Methods:From July to December 2021, Yanzhou District of Jining City, Ningyang County of Taian City, and Dongying District of Dongying City were selected as surveillance sites to investigate the population and distribution range of Pomacea spp., live snail samples were collected for morphological and genetic identification, and Pomacea spp. infected with the larva of Angiostrongylus cantonensis was detected by lung test. At the same time, sentinel hospital case surveillance was carried out in Yanzhou District, Jining City, and questionnaire was used to study the local residents' awareness of angiostrongyliasis cantonensis and their personal health behaviors. Results:A total of 312 live snail samples were collected. After morphological identification, they were all Pomacea spp.. After gene sequencing, two populations of Pomacea canaliculata and Pomacea maculata were found. No positive snails infected with Angiostrongylus cantonensis were found. A total of 126 patients with headache as the main neurological symptom were admitted to the sentinel hospital, but there were no monitoring cases that met the inclusion criteria. Among the survey population, 48.38% (134/277) of the respondents had heard of angiostrongyliasis cantonensis, 44.77% (124/277) knew that eating Margarya melanioides might cause angiostrongyliasis cantonensis, and 83.39% (231/277) had no related unhealthy eating behavior. Conclusion:Pomacea spp. is found and reported for the first time in Shandong Province, and there is a risk of population infection with angiostrongyliasis cantonensis.
5.Mechanism of LncRNA-ANCR expression and cellular malignant proliferation in human glioma tissues and cells
Haitao WANG ; Ying SU ; Xiubin HAN ; Xiangquan KONG ; Peng XU
Chinese Journal of Endocrine Surgery 2022;16(3):367-371
Objective:To investigate the expression of LncRNA ANCR in human glioma tissues and its relationship with malignant proliferation of cells.Methods:The samples of 10 normal brain tissue,13 low-grade and 45 high-grade gliomas were regarded as normal group, low-grade group and high-grade group, which were collected from neurosurgery department in Linyi Central Hospital, and the expression of ANCR and potential interaction molecule eIF4B was detected by reverse transcription polymerase chain reaction (RT-PCR) in vitro. Lentivirus transfection in vitro was used to construct the U251 shRNA ANCR and control cell line in human high-grade gliomas as control, test 1 and test 2 group cells in the study. QPCR detect the expression level ANCR, eIF4B and Myc mRNA in cells. Western blot was used to detect the expression of eIF4B and c-Myc protein, CCK-8 assay was used to detect the relative proliferation ability of cells, and the colony formation assay was used to observe the change of cell clone formation. SPSS 21.0 was used for statistical analysis, analysis of variance was used for inter group comparison, and SNK-q pairwise comparison method was used for intra group comparison.Results:The expressions of ANCR mRNA in high-grade glioma tissues, low-grade gliomas and normal brain tissues were 0.710±0.125, 2.033±0.312 and 3.408±0.296. The expressions of eIF4B mRNA in high-grade glioma tissues, low-grade gliomas and normal brain tissues were 0.176±0.019, 0.268±0.022 and 0.426±0.028. The expression of ANCR and eIF4B in high-grade glioma tissues was higher than that in low-grade gliomas and normal brain tissues ( P<0.001). The expression of ANCR in low-grade glioma tissues was higher than that in normal brain tissues ( P=0.013). There was a significant positive correlation between the expression of ANCR and eIF4B in glioma tissues ( P<0.001) ; The expressions of ANCR mRNA in Control, test1 and test2 were 1.000±0.021, 0.202±0.057 and 0.300±0.016. The expressions of eIF4B mRNA were 1.000±0.078, 0.452±0.012 and 0.526±0.037, and the expressions of c-Myc mRNA were 1.000±0.053, 0.688±0.067 and 0.564±0.089. the expressions of ANCR, eIF4B and c-Myc mRNA and protein in test1 and test2 cells were significantly lower than those in the control group ( P<0.01) ; the proliferation of test1 and test2 groups were significantly decreased at 72h and 96h, and the ability of colony formation was significantly decreased ( P<0.001) . Conclusion:The expression of ANCR was significantly up-regulated in high-grade glioma tissues and positively correlated with the expression of eIF4B. Interference with ANCR in vitro could mediate the decrease of the expression of eIF4B and c-Myc mRNA and protein molecules, thereby inhibiting the proliferation of glioma cells.
6.Meta-analysis of the Efficacy and Safety of Echinocandins as Antifungal Agents in the Prevention of Invasive Candidiasis
Sha LI ; Libo DAI ; Haitao YAO ; Xudong KONG
China Pharmacy 2020;31(1):104-109
ABSTRACT OBJECTIVE:To systematically evaluate the efficacy and safety of echinococcins in the prevention of invasive candidiasis,and to provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,Embase, Medline,Cochrane library,CJFD,VIP and Wanfang database,randomized controlled trials(RCTs)about the effectiveness and safety of echinococcins (trial group) versus conventional fungal drugs (amphotericin B and triazole antifungal agents,control group)in the prevention of invasive candidiasis were collected during database establishment to Jul. 2019. After data extraction of clinical studies met inclusion criteria and quality evaluation with Cochrane system evaluator manual 5.0.2,Meta-analysis was performed for breakthrough invasive fungal infection rate,fungal infection mortality rate,all-cause mortality rate and the incidence of drug withdrawal due to adverse reactions by using Rev Man 5.2 statistical software. RESULTS:Totally 7 RCTs were included, involving 3 219 patients. Results of Meta-analyses indicated that the incidence of breakthrough invasive fungal infection [OR=0.58, 95%CI(0.40,0.85),P=0.004],fungal infection mortality rate[OR=0.68,95%CI(0.51,0.92),P=0.01] and the incidence of drug withdrawal due to adverse reactions [OR=0.52,95%CI(0.40,0.67),P<0.001] in trial groups were significantly lower than control group,with statistical significance. There was no statistical significance in the all-cause mortality rate [OR=0.84,95%CI(0.67, 1.05),P=0.13]. CONCLUSIONS:Compared with amphotericin B and triazole antifungal agents,echinococcins used for the prevention of invasive candidiasis can reduce the incidence of breakthrough invasive fungal infection,fungal infection mortality rate and the incidence of drug withdrawal due to adverse reactions
7.Study on the relationship between wholeGorgan MRI score (WORMS)and pain in patients with knee osteoarthritis
Cong MA ; Han CHEN ; Lichun QIU ; Qiang XU ; Dongqing WANG ; Haitao ZHU ; Qianqian KONG ; Lirong ZHANG
Journal of Practical Radiology 2019;35(6):943-947
Objective To investigate the correlation between wholeGorgan MRI score (WORMS)and pain in patients with knee osteoarthritis (OA).Methods 1 1 9 patients with knee OA were enrolled,and The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)was used to estimate the pain.Knees of all the subj ects underwent scanning with sagittal,coronal,transverse TSEG T2 WIGFS and sagittal 3DGFLASHGWE sequences at 3.0T MR.The pathological changes of knee cartilage lesions,subarticular bone marrow edema (BME),bone cysts,bone attrition,osteophytes,meniscal inj ury,ligament inj ury,synovial thickening and joint effusion were evaluated according to the WORMS.The correlations between the above pathological changes and the pain were analyzed.Results There were significant and positive correlations between articular cartilage lesions and osteophytes,articular cartilage lesions and BME,BME and cyst,bone attrition and osteophytes,and BME and osteophytes,with the correlation coefficients of 0.6 70,0.5 9 8,0.5 1 8,0.5 1 4 and 0.505 ,respectively (P<0.05 ).Multiple regression analysis showed that BME,bone attrition,synovial thickening and joint effusion were the main factors affecting the severity of pain after adj usted for age and BMI (P<0.05).Conclusion The source of OA pain is multifactorial.The severity of BME,bone attrition,synovial thickening and joint effusion are the main factors associated with joint pain.As a nonGinvasive examination method,MR can make a comprehensive evaluation of the pathological changes of knee OA.
8.Clinical analyses of twelve children with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation
Chengxiang KONG ; Xiaoyang HONG ; Yingyue LIU ; Ping JIN ; Xiaojuan ZHANG ; Zhe ZHAO ; Haitao GAO ; Zhichun FENG
Chinese Pediatric Emergency Medicine 2018;25(9):673-677
Objective To summarize the clinical experience of extrocorporeal membrane oxygena-tion(ECMO) in the treatment of pediatric acute respiratory distress syndrome (ARDS). Methods A retro-spective analysis of children with ARDS who were hospitalized for different causes and received the treatment of ECMO from October 2012 to November 2017 was performed. The clinical conditions and prognostic fac-tors in the course of their disease were compared. Results In 12 cases of ARDS,9 cases (75% ) had severe pneumonia,2 cases (16. 67% ) had lung tumor resection and 1 case ( 8. 33% ) had bronchial foreign body. Seven cases (58. 3% ) chose VA-ECMO,5 (41. 7% ) cases chose VV-ECMO. The average duration of ECMO was (225. 03 ± 214. 75) h. With the positive treatment of ECMO,heart rate,mixed venous oxygen saturation and central venous pressure all improved significantly(P < 0. 05),and there was no obvious abnor-mal changes in MAP and lactic acid(P > 0. 05). Arterial oxygen partial pressure,arterial carbon dioxide par-tial pressure,oxygenation index and P/ F were significantly improved after the ECMO support(P < 0. 05). Ppeak,Paw and PEEP after evacuation of ECMO were significantly lower than those before treatment (P <0. 05). Ten cases (83. 33% ) were successfully removed,8 cases (66. 67% ) were saved, and 4 cases (33. 33% ) died. During the ECMO treatment,9 cases (75% ) had complications,including 8 cases of bleed-ing at the intubation site,3 cases of gastrointestinal hemorrhage,2 cases of hemolysis,1 case of infection,2 cases of acute kidney injury,2 cases of neurological symptoms,1 case of multiple organ dysfunction syn-drome. Conclusion Pediatric ARDS is critical and the mortality rate is high. ECMO should be used as soon as possible when the lung is potentially regained and other treatments are ineffective,so that the lung could be fully rescued to gain time and opportunity for clinical treatment.
9.Correlation between axillary lymph node metastases and ultrasonographic characteristics of axillary lymph node combined with immunohistochemistry in breast cancer patients
Xiangchong KONG ; Wen CHENG ; Cunli GUO ; Haitao SHANG ; Na ZHANG
China Oncology 2016;26(2):155-160
Background and purpose:Axillary lymph node metastasis of breast cancer has an important significance in prognosis and treatment of breast cancer. This study was to investigate the correlation between axillary lymph node metastasis and ultrasonographic characteristics of axillary lymph node combined with immunohistochemistry in breast cancer patients.Methods:A total number of 366 breast cancer patients were selected in this study. Seven hundred and twenty-eight axillary lymph nodes were collected. With ultrasonography, the maximum cortex thickness, the ratio of the height to the length, the ratio of the cortex to the medulla and blood lfow of axillary lymph nodes were observed, in order to study the correlation between these indicators and axillary lymph node metastasis combined with the postoperative immunohistochemical results.Results:According to univariate analysis, axillary lymph node maximum cortex thickness, the ratio of the height to the length, characteristics of blood flow and the positive expression rate of p53 were related to axillary lymph node metastasis (P<0.05). Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve showed that axillary lymph node maximum cortex thickness was the best indicator to determine axillary lymph node metastasis. The positive expression rate of p53 in patients with maximum cortex thickness >3 mm (42.78%) of axillary lymph node was signiifcantly higher than that in patients with maximum cortex thickness≤3 mm (25.82%) (P<0.01).Conclusion:Ultrasonographic characteristics of axillary lymph node and immunohistochemistry method are closely correlated with axillary lymph node metastasis in patients with breast cancer, which is important in diagnostic and treatment in clinic.
10.Changes of Erythropoietin and Hemorheology in OSAHS Patients under Positive Pressure Ventilation Intervention
Kaifeng DONG ; Jing XUE ; Zhiming LIU ; Xin LYU ; Jihua ZHANG ; Haitao XUE ; Xiangling KONG ; Caili HAN
Tianjin Medical Journal 2014;(8):786-789
Objective To observe changes of erythropoietin (EPO) and rheology in moderate and severe obstructive sleep apnea hypopnea syndrome (OSAHS) patients after the noninvasive positive pressure ventilation (NPPV) treatment. Methods Healthy adults were selected as control group (n=40) while moderate to severe OSAHS patients were selected as OSAHS group. OSAHS group was underwent NPPV treatment then, Levels of sleep apnea hypopnea index (AHI), sleep mean minimum oxygen saturation (LSaO2) and serum erythropoietin (EPO) were assessed, routine blood test and hemodynam-ic indexes were also checked before treatment and 1 and 3 months after treatment in both groups. Results In both groups serum EPO, blood, blood rheology indexes, AHI, LSaO2 were analysised at each time point by ANOVA repeated measures, all of which show significant different between groups and between each time points within the same group. Indexes in OSAHS group improved with prolonged treatment , but they are in the normal range in the control. Conclusion OSAHS pa-tients with NPPV therapy can significantly relieve hypoxia, reduce serum EPO level and blood viscosity. So NPPV has impor-tant clinical significance in prevention and treatment of OSAHS.

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